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- CMV infection of liver transplant recipients: comparison of antigenemia and molecular biology assays.Publication . Amorim, M.; Cabeda, J.; Seca, R.; Mendes, A.; Castro, A.; Amorim, J.Abstract BACKGROUND: CMV is a major clinical problem in transplant recipients. Thus, it is important to use sensitive and specific diagnostic techniques to rapidly and accurately detect CMV infection and identify patients at risk of developing CMV disease. In the present study, CMV infection after liver transplantation was monitored retrospectively by two molecular biology assays - a quantitative PCR assay and a qualitative NASBA assay. The results were compared with those obtained by prospective pp65 antigenemia determinations. MATERIALS AND METHODS: 87 consecutive samples from 10 liver transplanted patients were tested for CMV by pp65 antigenemia, and CMV monitor and NASBA pp67 mRNA assay. RESULTS: CMV infection was detected in all patients by antigenemia and CMV monitor, whereas NASBA assay identified only 8/10 patients with viremia. Furthermore, CMV infection was never detected earlier by molecular biology assays than by antigenemia. Only 5/10 patients with CMV infection developed CMV disease. Using a cut off value of 8 cells/50,000, antigenemia was found to be the assay that better identified patients at risk of developing CMV disease. However, the kinetics of the onset of infection detected by NASBA and CMV monitor seemed to have better identified patients at risk of developing CMV disease. Furthermore, before onset of disease, CMV pp67 mRNA was found to have similar or better negative and positive predictive values for the development of CMV disease. CONCLUSIONS: The present data, suggests that the concomitant use of antigenemia and pp67 mRNA assay gives the best identification of patients at risk of developing CMV disease.
- Pneumonite intersticial crónicaPublication . Almeida, R.; Reis, G.; Ferreira, C.; Oliveira, M.; Oliveira, D.; Fernandes, P.; Ferreira, P.; Frutuoso, S.; Carreira, L.; Alves, V.; Paiva, A.; Guedes, M.A patologia pulmonar intersticial compreende um grupo de doenças crónicas caracterizadas por alterações das paredes alveolares e perda das unidades funcionais alveolocapilares. São doenças raras nas crianças, na sua maioria de causa desconhecida e revestindo-se habitualmente de uma elevada morbimortalidade, dada a pouca eficácia da terapêutica actualmente disponível. Os autores descrevem o caso clínico de uma criança de 3 anos, previamente saudável, que no contexto de uma infecção respiratória desenvolve um quadro de sibilância e insuficiência respiratória grave, na investigação do qual é diagnosticada uma pneumonite intersticial crónica. Foram tentadas diversas terapêuticas (corticoterapia sistémica, hidroxicloroquina, N-acetilcisteína) sem melhoria evidente.Interstitial lung disease includes a group of chronic diseases characterized by alterations in alveolar walls and loss of functional alveolar-capillary units. These are rare diseases in children, mostly with an unknown cause and associated with a high morbidity and mortality due to insufficient therapeutic effectiveness. The authors report a case of a previously healthy 3 years old child who presented with wheezing and severe respiratory insufficiency following a respiratory infection. The investigation performed led to the diagnosis of chronic interstitial pneumonitis. Several treatments have been tried (corticosteroids,hydroxychloroquine, N-acetylcysteine) without any obvious improvement.
- Biópsia Renal Percutânea: experiência de oito anosPublication . Castro, R.; Sequeira, M.; Faria, M.; Belmira, A.; Sampaio, S.; Roquete, P.; Silvestre, F.; Rocha, C.; Morgado, T.A biópsia renal constitui um instrumento fundamental para o diagnóstico e prognóstico de diversas patologias nefrológicas e sistémicas. No nosso Hospital a sua realização iniciou-se em 1994, tendo sido biopsado um doente com Doença de Berger. Até à data foram efectuadas 91 biópsias renais percutâneas com a seguinte distribuição anual: 1994 (n=3), 1995 (n=3), 1996 (n=3), 1997 (n=15), 1998 (n=5), 1999 (n=23), 2000 (n=13), 2001 (n=26) em 57 homens e 34 mulheres. Foi utilizada orientação ecográfica e na maioria dos casos a agulha de Vim Silverman (14G). Apenas em cinco casos se utilizou uma pistola automática BARD. Era nosso objectivo, em cada biópsia, a colheita de pelo menos dois fragmentos, um para microscopia óptica e outro para imunoflurescência. Os grandes síndromas nefrológicos que conduziram a este exame foram: síndroma nefrótico (n=27), anormalidades urinárias assintomáticas (n=25), insuficiência renal aguda ou rápidamente progressiva (n=18), insuficiência renal crónica (n=15), hipertensão arterial (n=4) e glomerulonefrite aguda (n=2). Em 92.3% (84/91) dos casos foi possível efectuar um diagnóstico histológico por microscopia óptica. Se considerarmos, no entanto, sete casos com suspeita clínica de nefropatia IgA em que o fragmento colhido para imunoflurescência não continha glomérulos, a eficácia diminuiu para 84.6% (77/91). O número médio de glomérulos por amostra foi de 18.3 ± 14.2 [0-80]. Os diagnósticos histológico obtidos foram os seguintes: doença de Berger (n=24), diversas formas de síndroma nefrótico primário (n=18), nefrite lúpica (n=8), glomerulonefrite mesangioproliferativa, sem glomérulos na imunoflurescência (n=6), ausência de tecido renal ou de glomérulos nas amostras (n=6), síndroma nefrótico secundário (n=4), nefrite túbulo-intersticial ou necrose tubular aguda (n=4), nefropatia diabética (n=3), rim de mieloma (n=3), glomerulonefrite crescêntica sem depósitos imunes (n=3), nefroangiosclerose hipertensiva (n=2), glomerulonefrite mesangioproliferativa IgM (n=2) e outros (n=8). A hematúria macroscópica revelou-se como a complicação mais frequente (n=9; 9.9%). Apenas em três casos se verificou a existência de hematoma renal ecograficamente (3.3%). A saída de sangue pelo mandril da agulha de biópsia surgiu em quatro casos (4.4%) e foi necessário proceder à transfusão de concentrado de glóbulos rubros em três doentes (3.3%). Registamos uma punção acidental de baço. Em nenhum caso foi necessário efectuar nefrectomia por hemorragia incontrolável. Identificamos, como índices de mau prognóstico relativamente à evolução para insuficiência renal crónica avançada (n=2) ou terminal (n=15), o maior número de glomérulos esclerosados (30% vs 8%; p<0.01) e de lesões túbulo-intersticiais (100% vs 63%; p<0.01). Em conclusão, a biópsia renal efectuada com orientação ecográfica permitiu a obtenção 21 de amostras com valor diagnóstico em 84.6% dos casos. A taxa de complicações foi relativamente baixa comparando com outras séries. Verificamos um progressivo aumento de qualidade das amostras renais colhidas, em relação directa com uma coordenação técnica crescente entre os nefrologistas e radiologistas intervenientes.nephrological and systemic pathologies. At our institution the first patient submitted to this technique, at 1994, showed Berger disease. Until 2002 we have performed 91 renal biopsies (57 men and 34 women) with the following annual distribution: 1994 (n=3), 1995 (n=3), 1996 (n=3), 1997 (n=15), 1998 (n=5), 1999 (n=23), 2000 (n=13) and 2001 (n=26). Ultrasound guidance was always used and in most of cases the technique was performed with Vim-Silverman (14G) needle. BARD automatic system was employed in only five patients. The clinical diagnosis that lead to renal biopsy were: nephrotic syndrome (n=27), asyntomatic urinary abnormalities (n=25), acute or rapidly progressive renal failure (n=18), chronic renal failure (n=15), hypertension (n=4) and acute nephritis (n=2). The efficacy for optic histological diagnosis was 92.3% (84/91). However, if we include seven cases of presumed IgA nephropathy that don’t included fragment for immunofluorescence (IF) analysis the efficacy declined to 84.6% (77/91). The mean number of glomeruli per fragment was 18.3 ± 14.2 [0-80]. Histological diagnosis were the following: Berger disease (n=24), idiopathic nephrotic syndrome (n=18), lupus nephritis (n=8), mesangial proliferative glomerulonephritis without glomeruli in the IF fragment (n=6), without glomeruli (n=6), secondary nephrotic syndrome (n=4), tubulointerstitial nephritis or acute tubular necrosis (n=4), diabetic nephropathy (n=3), myeloma kidney (n=3), pauci-imune and crescentic glomerulonephritis (n=3), hypertensive nephropathy (n=2), IgM mesangial proliferative glomerulonephritis (n=2) and various (n=8). Gross hematuria appeared in 9 patients (9.9%). Only in three of these patients it was showed, by ecography, the existence of kidney haematoma. Bleeding throughout the mandrill in four cases, leaded to transfusion in only three patients. We have registered one accidental spleen puncture. Nephrectomy for incontrollable bleeding was never needed. Higher glomerulosclerosis (30% vs 8%; p<0.01) and also a greater extent of tubulointersticial lesions (100% vs 63%; p<0.01), were predictors of progression into end-stage or advanced renal failure. Concluding, renal biopsy with ultrasound guidance was valuable for diagnosis in 84.6% of our proceedings. Our serie is similar to others concerning serious complications. Nephrologists and radiologists improved progressively their coordination performing this technique, improving the results during this period of 8 years.
- IMPORTÂNCIA DA CITOMETRIA DE FLUXO NA AVALIAÇÃO DE LESÕES CEREBRAIS SUSPEITAS DE LINFOMAPublication . Campos, F.; Bini-Antunes, M.; Santos, A.; Queirós, M.; Santos, M.; Gonçalves, M.; Fonseca, S.; Lau, C.; Teixeira, M.; Nunes, P.; Pinheiro, C.; Pires, M.; Lima, M.A citometria de fluxo (CF) tem adquirido um papel cada vez maior no diagnóstico e classificação das patologias linfoproliferativas, sendo fundamental a integração e complementaridade das informações obtidas por citometria com os resultados do estudo anatomo-patológico (EAP). Existem, porém, escassas referências na literatura que documentem a importância da CF na avaliação de lesões cerebrais suspeitas de linfoma.
- UpdatIng Course on Anatomic PathologyPublication . Serviço de Anatomia Patológica do CHPCourse Description: We are pleased to announce the 1st edition of our course entitled “Curso de Actualização em Anatomia Patológica Centro Hospitalar do Porto 2012”. The course is organized by Centro Hospitalar do Porto, Porto [Portugal] and shall provide the highest level of subspecialty instruction by a distinguished faculty recognized in the fields of Anatomic Pathology. The educational event shall include 3 days of anatomic pathology theoretical and practical sessions related to breast, salivary gland, lymphomas, bone and soft tissues, cutaneous melanocytic lesions and pleuropulmonary and mediastinal areas, highlighting diagnostic challenges, illustrating potential pitfalls and how to avoid them, and highlighting the role of complementary molecular techniques and their application in patient care. The surgical pathology blocks will be anticipated by corresponding clinical satellite conferences, giving emphasis on National contributions. The greatest educational feedback is expected for community hospital physicians, in particular, pathologists and residents. The course goal is to provide participants with practical and meaningful information relevant to diagnostic task, prognostic assessment and therapy guidance of cancer patients. The course is intended for a broad audience; however, it is primarily designed for pathologists devoting most of their efforts to practical surgical pathology. Course organizers encourage the participation of anatomic pathology, general and thoracic surgery, dermatology, ENT and oncology residents
- Lesão Renal Aguda e Rabdomiólise como Apresentação da Doença de McardlePublication . Costa, R.; Castro, R.; Costa, A.; Taipa, R.; Vizcaíno, J.; Morgado, T.A doença de McArdle apresenta-se tipicamente por mialgias, intolerância aos esforços, cãibras e mioglobinúria na infância ou jovens adultos. A deficiência hereditária da enzima miofosforílase incapacita a degradação de glicogénio, com consequente acumulação no tecido muscular e défice energético. A rabdomiólise pode ocorrer e complicar-se de lesão renal aguda mas raramente, em cerca de 11% dos casos, é manifestação inicial da doença. Apresentamos um caso de Doença de McArdle num paciente de 38 anos de idade. Tinha antecedentes de mialgias, intolerância aos esforços e episódio isolado de mioglobinúria. A doença foi diagnosticada num episódio de rabdomiólise grave complicada de lesão renal aguda oligúrica, com necessidade de hemodiálise. A biópsia renal demonstrou necrose tubular aguda. Apesar da recuperação renal, os marcadores de lise muscular permaneceram elevados. Na suspeita de miopatia metabólica realizou biópsia muscular que revelou deposição subsarcolémica de glicogénio e ausência de atividade da miofosforilase. As miopatias metabólicas devem ser consideradas na abordagem de LRA associada a rabdomiólise severa.
- Tumor regression grades: can they influence rectal cancer therapy decision tree?Publication . Santos, M.; Silva, C.; Rocha, A.; Matos, E.; Nogueira, C.; Lopes, C.BACKGROUND: Evaluating impact of tumor regression grade in prognosis of patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: We identified from our colorectal cancer database 168 patients with LARC who received neoadjuvant therapy followed by complete mesorectum excision surgery between 2003 and 2011: 157 received 5-FU-based chemoradiation (CRT) and 11 short course RT. We excluded 29 patients, the remaining 139 were reassessed for disease recurrence and survival; the slides of surgical specimens were reviewed and classified according to Mandard tumor regression grades (TRG). We compared patients with good response (Mandard TRG1 or TRG2) versus patients with bad response (Mandard TRG3, TRG4, or TRG5). Outcomes evaluated were 5-year overall survival (OS), disease-free survival (DFS), local, distant and mixed recurrence. RESULTS: Mean age was 64.2 years, and median followup was 56 months. No statistically significant survival difference was found when comparing patients with Mandard TRG1 versus Mandard TRG2 (p = .77). Mandard good responders (TRG1 + 2) have significantly better OS and DFS than Mandard bad responders (TRG3 + 4 + 5) (OS p = .013; DFS p = .007). CONCLUSIONS: Mandard good responders had a favorable prognosis. Tumor response (TRG) to neoadjuvant chemoradiation should be taken into account when defining the optimal adjuvant chemotherapy regimen for patients with LARC
- A lactate shuttle system between tumour and stromal cells is associated with poor prognosis in prostate cancerPublication . Pértega-Gomes, N.; Vizcaíno, J.; Attig, J.; Jurmeister, S.; Lopes, C.; Baltazar, F.BACKGROUND: In a malignant tumour, cancer cells are embedded in stromal cells, namely cancer-associated fibroblasts (CAFs). These CAFs are now accepted as important players in cancer dynamics, being involved in tumour growth and progression. Although there are various reports on the interaction between tumour and stromal cells, the clinico-pathological significance of this cross-talk is still largely unknown. In this study, we aimed to characterise the expression of key metabolic proteins involved in glucose transport, pyruvate/lactate shuttle system, glycolytic metabolism and fatty acid oxidation in CAFs and tumour cells in different stages of malignant transformation. We further aimed to contextualise the clinico-pathological significance of these protein expression profiles with reference to known prognostic indicators, including biochemical recurrence in pT stage. METHODS: Prostate tissues were obtained from 480 patients with a median age of 64 years following radical prostatectomy with no previous hormonal therapy. Tissues were analysed for the expression of several key metabolism-related proteins in glands and surrounding fibroblasts by immunohistochemistry. Reliable markers of prognosis such as pT stage and biochemical recurrence were assessed for each case. RESULTS: We observed that prostate cancer cells did not rely mainly on glycolytic metabolism, while there was a high expression of MCT4 and CAIX - in CAFs. This corroborates the hypothesis of the "Reverse Warburg effect" in prostate cancer, in which fibroblasts are under oxidative stress and express CAIX, an established hypoxia marker. We found that alterations in the expression of metabolism-related proteins were already evident in the early stages of malignant transformation, suggesting the continuing alteration of CAFs from an early stage. Additionally, and for the first time, we show that cases showing high MCT4 expression in CAFs with concomitant strong MCT1 expression in prostate cancer (PCa) cells are associated with poor clinical outcome, namely pT3 stage of the tumour. CONCLUSIONS: In summary, this work demonstrates for the first time the clinico-pathological significance of the lactate shuttle in prostate cancer. It also suggests that other alterations in CAFs may be useful prognostic factors, and further supports the use of MCT1/MCT4 as targets for PCa therapy.
- Membranoproliferative glomerulonephritis associated with type II cryoglobulinaemia in a renal transplant patient with hepatitis CPublication . Bento, C.; Malheiro, J.; Almeida, M.; Martins, L.; Dias, L.; Vizcaíno, J.; Castro-Henriques, A.The most common HCV-related nephropathy is membranoproliferative glomerulonephritis (MPGN), usually in the context of cryoglobulinaemia. The treatment of this entity is not consensual and represents a challenge to clinicians. We report a case of membranoproliferative glomerulonephritis associated with cryoglobulinaemia type II in a 46-year-old Caucasian male recipient of a deceased kidney transplant in 2010. His baseline serum creatinine (SCr) was 1.1 mg/dl. After three years post-transplantation, he presented with nephritic syndrome in association with renal function impairment (SCr – 2.1 mg/dl). The laboratory tests revealed positive rheumatoid factor, hypocomplementaemia and a positive cryocrit with type II cryoglobulinaemia. Antinuclear autoantibodies and anti-double stranded DNA antibodies were negative. Despite the presence of anti-HCV antibodies, the viral load remained undetectable. The allograft biopsy showed lesions compatible with membranoproliferative glomerulonephritis, with staining in the immunofluorescence for granular IgM and C3 and no C4d. He was treated with methylprednisolone pulses followed by oral prednisolone in association with rituximab. Two months after the last dose of rituximab, the SCr improved to 1.27 mg/dl, the proteinuria decreased and serum C3 levels normalized. Cryogloglobulins and rheumatoid factor became negative and HCV RNA remained undetectable. The patient was lost for follow-up. In our case, the treatment with rituximab resulted in a favourable outcome, although a longer follow-up period may be needed to evaluate the clinical response, since other studies reported high relapse rates.
- Mesalazine induced tubulointersticial nephritisPublication . Campos, A.; Santos, S.; Santos, J.; Malheiro, J.; Lobato, L.; Vizcaíno, J.; Cabrita, A.Inflammatory bowel disease and its various treatments may affect the kidney in several ways tubulointersticial nephritis is a rare but serious complication of longer-term mesalazine use. There are few cases reported in the literature. We report the first two cases of mesalazine-induced tubulointersticial nephritis, recently diagnosed in our department. The first one refers to a patient with ulcerous colitis and the second one to a patient with Crohn’s disease. Then the authors present a review of literature about the renal involvement in the inflammatory bowel disease. New cases of mesalazine nephrotoxicity should be reported to allow more accurate incidence estimation of this serious adverse effect. Routine monitoring of renal function is simple, inexpensive and allows an early diagnosis of this complication